Izzi Valerio, Lakkala Juho, Devarajan Raman, Kääriäinen Anni, Koivunen Jarkko, Heljasvaara Ritva, Pihlajaniemi Taina
Oulu Center for Cell-Matrix Research and Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland.
Centre for Cancer Biomarkers (CCBIO), Department of Biomedicine, University of Bergen, N-5009 Bergen, Norway.
Matrix Biol Plus. 2019 Apr 6;1:100004. doi: 10.1016/j.mbplus.2019.04.001. eCollection 2019 Feb.
The microenvironment plays a central role in cancer, and neoplastic cells actively shape it to their needs by complex arrays of extracellular matrix (ECM) proteins, enzymes, cytokines and growth factors collectively referred to as the matrisome. Studies on the cancer matrisome have been performed for single or few neoplasms, but a more systematic analysis is still missing. Here we present a Pan-Cancer study of matrisome gene expression in 10,487 patients across 32 tumor types, supplemented with transcription factors (TFs) and driver genes/pathways regulating each tumor's matrisome. We report on 919 TF-target pairs, either used specifically or shared across tumor types, and their prognostic significance, 40 master regulators, 31 overarching regulatory pathways and the potential for druggability with FDA-approved cancer drugs. These results provide a comprehensive transcriptional architecture of the cancer matrisome and suggest the need for development of specific matrisome-targeting approaches for future therapies.
微环境在癌症中起着核心作用，肿瘤细胞通过细胞外基质（ECM）蛋白、酶、细胞因子和生长因子等复杂组合，根据自身需求积极塑造微环境，这些统称为基质组。针对单一或少数几种肿瘤开展了癌症基质组研究，但仍缺乏更系统的分析。在此，我们对32种肿瘤类型的10487例患者的基质组基因表达进行了泛癌研究，并补充了调节每种肿瘤基质组的转录因子（TFs）和驱动基因/通路。我们报告了919个TF-靶标对，这些对在肿瘤类型中要么是特异性使用的，要么是共享的，及其预后意义、40个主要调节因子、31条总体调节通路以及FDA批准的癌症药物的可成药潜力。这些结果提供了癌症基质组的全面转录结构，并表明未来治疗需要开发针对特定基质组的靶向方法。
